The precise mechanism of herpes simplex virus (HSV) entry into cells is still far from understood. Five envelope glycoproteins, gB, gC, gD and gH-gL are required. Ceil surface heparan sulfate proteoglycans provide attachment sites for the virus by interacting with gB and/or gC. Subsequent to that, recently discovered gD receptors mediate fusion of the viral envelope with the cell plasma membrane and are absolutely required for entry. The role of gH-gL, although known to be essential for entry, is not defined. Previously, gH was thought to be expressed on the cell surface in the presence of gL, however, our recent findings report a gH-mediated viral entry interference phenomenon. Preliminary data suggests that HS may be involved in the gH-mediated interference. In light of these new findings, we propose to study gH-mediated interference and the potential interaction between HSV-1 gH and HS. My thesis research is expected focus on the following two aims: 1: Determine the specificity of gH-mediated interference. 2: Determine if gH-mediated interference is caused by heparan sulfate.